DNA-SEQUENCES IN THE PROMOTER REGION OF THE NF1 GENE ARE HIGHLY CONSERVED BETWEEN HUMAN AND MOUSE

The gene for type 1 neurofibromatosis (NF1) is most highly expressed i n brain and spinal cord, although low levels of mRNA can be found in n early all tissues. As a first step in investigating the regulation of NF1 gene expression, we have cloned and sequenced the promoter regions of the human and mouse NF1 genes and mapped the transcriptional start sites in both species. We report here that the 5' ends of the human a nd murine NF1 genes are highly conserved. While no discernable TATA or CCAAT box sequences are seen, transcription initiates at identical si tes in both species, 484 nucleotides upstream of the ATG initiation co don in the human gene. The human and mouse NF1 genes share particularl y high sequence homology (95%) between nucleotides -33 and +261 and co ntain several perfectly conserved transcription factor binding site mo tifs, including a cAMP response element, several AP2 consensus binding sites, and a serum response element. The high conservation of these s equences indicates that they are likely to be significant in the regul ation of NF1 gene expression. (C) 1994 Academic Press, Inc.